21 results on '"Nadav Sarid"'
Search Results
2. Characteristics and outcomes of adults with cytomegalovirus‐associated thrombocytopenia: a case series and literature review
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David Varon, Tamir Shragai, Nadav Sarid, Irit Avivi, Ilya Kirgner, Eyal Lebel, and Dana Deshet
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Adult ,Male ,medicine.medical_specialty ,Thrombopoietin Receptor Agonists ,Congenital cytomegalovirus infection ,Cytomegalovirus ,Antiviral Agents ,Asymptomatic ,Virus ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,Child ,Aged ,Aged, 80 and over ,Response rate (survey) ,Hematology ,Atypical Lymphocyte ,business.industry ,Middle Aged ,medicine.disease ,Thrombocytopenia ,030220 oncology & carcinogenesis ,Cytomegalovirus Infections ,Elevated transaminases ,Female ,Steroids ,medicine.symptom ,business ,Receptors, Thrombopoietin ,030215 immunology - Abstract
Cytomegalovirus (CMV) is a ubiquitous virus that infects people worldwide. CMV is known to trigger thrombocytopenia, but this association is probably underdiagnosed since CMV infection in healthy adults is usually either asymptomatic or causes only mild symptoms. A systematic literature review was carried out and yielded 23 publications that reported 25 patients. All haematology centres in Israel were searched for adult immunocompetent patients with CMV-associated thrombocytopenia, and five new cases were identified. The median age of the combined 30 patients was 33 years (range 18-80), 73% were men, 77% presented with CMV-related symptoms, 48% had enlarged spleens, 95% had atypical lymphocytes in peripheral blood and 68% had elevated transaminase levels. The response rate to first-line steroid-containing regimens was only 31%, whereas 11 patients who were treated with an anti-CMV agent had a response rate of 82%. Moreover, four patients received thrombopoietin receptor agonists (TPO-RA) to which three (75%) responded. Taken together, these distinctive features of a case with thrombocytopenia should alert to CMV infection as the source. While steroids were effective in less than one-third of the cases, both anti-CMV therapy and TPO-RA exhibited excellent efficacy, suggesting that those agents should be introduced earlier in the therapeutic course.
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- 2020
3. Radiotherapy in mantle cell lymphoma: A literature review
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John Kuruvilla, Eva Yashphe, Sharon Ben Barouch, Richard W. Tsang, and Nadav Sarid
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Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Lymphoma, Mantle-Cell ,Disease ,Malignancy ,Systemic therapy ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Toxicity profile ,Radiotherapy ,business.industry ,Distant disease ,Low dose ,Hematology ,General Medicine ,Prognosis ,medicine.disease ,Radiation therapy ,030220 oncology & carcinogenesis ,Mantle cell lymphoma ,business ,030215 immunology - Abstract
Mantle cell lymphoma (MCL) is a B-cell malignancy, comprising between 3% and 10% of all adult-onset non-Hodgkin lymphomas. MCL is considered incurable with current treatment modalities and most patients require multiple lines of treatment during their lifetime. MCL is very sensitive to radiotherapy (RT), even when delivered in low doses. In limited-stage MCL, RT can enable the de-escalation of systemic therapy. RT monotherapy is a valid option for frail patients. In advanced-stage disease, RT is very potent mode of palliation, even in heavily pretreated and chemo-resistant patients. Furthermore, it can provide a respite during which systemic treatment is unnecessary. In general, RT has a favorable toxicity profile and can be repeated as necessary for local relapse or distant disease. This effective, safe, and relatively inexpensive modality of therapy has been underutilized for patients with MCL. In this review, we will outline the use of RT for limited and advanced-stage disease and its potential application in combination with novel drugs.
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- 2020
4. Characteristics, management and outcome of DLBCL patients, presenting with simultaneous systemic and CNS disease at diagnosis: A retrospective multicenter study
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Chava Perry, Avraham Avigdor, Noa Lavi, Ron Ram, Lev Shvidel, Sharon Ben Barouch, Neta Goldschmidt, Orit Sofer, Osnat Bairey, Eyal Lebel, Nadav Sarid, Irit Avivi, Netanel A. Horowitz, and Yair Herishanu
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Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Gastroenterology ,Disease-Free Survival ,Central Nervous System Neoplasms ,03 medical and health sciences ,0302 clinical medicine ,Autologous stem-cell transplantation ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Autologous transplantation ,Anthracyclines ,Progression-free survival ,Survival rate ,Aged ,Aged, 80 and over ,Chemotherapy ,business.industry ,Cytarabine ,Hematology ,Middle Aged ,medicine.disease ,Survival Rate ,Methotrexate ,030220 oncology & carcinogenesis ,Concomitant ,Female ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,030215 immunology ,medicine.drug - Abstract
The incidence of systemic diffuse large B cell lymphoma (DLBCL) concurrently involving the central nervous system (CNS) at diagnosis, is very low and data regarding the clinical course of these patients are scarce. We investigated characteristics, efficacy of treatment regimens including consolidative autologous stem cell transplantation and outcome of patients presenting with concomitant systemic and CNS DLBCL. The records of 44 patients, diagnosed between 2004 and 2017, who fulfilled the inclusion criteria, were retrospectively reviewed. CNS involvement was diagnosed as solely parenchymal in 41%, solely leptomeningeal in 43%, and paranchymal with leptomeningeal in 11% of the patients. Induction regimens were anthracycline-based combined with high-dose methotrexate (HD-MTX) in 80% (n = 35) of patients, anthracycline-based combined with intrathecal MTX in 3, cytarabine-based (without antracyclines) in 2, HD-MTX in 1 and palliative in three. Five of 41 patients treated with chemotherapy died of treatment-related toxicity, all due to infections. Nineteen patients had consolidative autologous transplantation. Overall response rate following induction was 80% (complete responses 66% and partial responses 15%). All relapses (n = 11) occurred within less than 2 years. Within a median follow-up of 26.8 months, 3-years projected overall survival (OS) and progression free survival rates for the entire cohort were 56% ± 8.3 and 42% ± 8.9, respectively. In multivariate analysis, RCHOP-HD MTX-based induction [HR = 0.228, (0.054-0.964)], administration of 3.5 g/m2 MTX [HR = 0.735 (0.620-0.871)], and attaining CR following induction [HR = 0.185, (0.051-0.667)] predicted longer OS. RCHOP-HD MTX can provide prolonged remissions in DLBCL patients presenting with concomitant systemic and CNS involvement whereas role of autograft remains uncertain.
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- 2019
5. Toxicity and efficacy of chimeric antigen receptor T-cell therapy in patients with diffuse large B-cell lymphoma above the age of 70 years compared to younger patients - a matched control multicenter cohort study
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Ronit Gurion, Yaeli Bar-On, Liat Shargian-Alon, Sigi Kay, David Hagin, Ronit Gold, Irit Avivi, Polina Stepensky, Batia Avni, Moshe Yeshurun, Nadav Sarid, Chava Perry, Ron Ram, Sigal Grisariu, Odelia Amit, Chen Glait-Santar, and Yair Herishanu
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medicine.medical_specialty ,T cell ,Antigens, CD19 ,Cell- and Tissue-Based Therapy ,Receptors, Antigen, T-Cell ,Immunotherapy, Adoptive ,Refractory ,Median follow-up ,Internal medicine ,medicine ,Humans ,Lymphoma, Follicular ,Aged ,Receptors, Chimeric Antigen ,business.industry ,Incidence (epidemiology) ,Hematology ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Toxicity ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,CD8 ,Cohort study - Abstract
Data regarding efficacy and toxicity of chimeric antigen receptor T (CAR-T) cell therapy in the elderly, geriatric population are insufficient. In 2019, tisagenlecleucel and axicabtagene-ciloleucel were commercially approved for relapsed/refractory diffuse large B-cell lymphoma. From May 2019 onwards, 47 relapsed/refractory diffuse large Bcell lymphoma patients, ≥70 years underwent lymphopharesis in three Israeli centers. Elderly (n=41, mean age 76.2 years) and young (n=41, mean age 55.4 years) patients were matched based on ECOG performance status and lactose dehydrogenase levels. There were no differences in CD4/CD8 ratio (P=0.94), %CD4 naive (P=0.92), %CD8 naive (P=0.44) and exhaustion markers (both HLA-DR and PD-1) between CAR-T cell products in both cohorts. Forty-one elderly patients (87%) received CAR-T cell infusion. There were no differences in the incidence of grade ≥3 cytokine-release-syndrome (P=0.29), grade≥3 neurotoxicity (P=0.54), and duration of hospitalization (P=0.55) between elderly and younger patients. There was no difference in median D7-CAR-T cell expansion (P=0.145). Response rates were similar between the two groups (complete response 46% and partial response 17% in the elderly group, P=0.337). Non-relapse mortality at 1 and 3 months was 0 in both groups. With a median follow-up of 7 months (range, 1.3-17.2 months), 6- and 12-months progression-free and overall survival in elderly patients were 39% and 32%, and 74% and 69%, respectively. EORTC QLQ-C30 questionnaires, obtained at 1 month, showed worsening of disability and cancer-related-symptoms in elderly versus younger patients. We conclude that outcomes of CAR-T cell therapy are comparable between elderly, geriatric and younger patients, indicating that age as per se should not preclude CAR-T cell administration. Longer rehabilitation therapy is essential to improve disabilities and long-term symptoms.
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- 2021
6. Outcome of relapsed/refractory diffuse large B-cell lymphoma patients treated with polatuzumab vedotin-based therapy: real-life experience
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Noam Benyamini, Miri Zektser, Odit Gutwein, Nadav Sarid, Gilad Itchaki, Anatoly Nemets, Uri Abadi, Nagib Dally, Shimrit Harlev, Kalman Filanovsky, Elena Ribakovsky, Merav Leiba, Netanel A Horwitz, Ron Ram, Chava Perry, Ronit Gurion, Abraham Avigdor, Orit Sofer, Irit Avivi, Yafit Segman, Neta Goldschmidt, Tamar Tadmor, Yair Herishanu, Vladimir Vainstein, and Yair Goldhecht
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Oncology ,Cancer Research ,medicine.medical_specialty ,Immunoconjugates ,Clinical study ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Aged ,Retrospective Studies ,business.industry ,Antibodies, Monoclonal ,Retrospective cohort study ,Hematology ,medicine.disease ,humanities ,Lymphoma ,Polatuzumab vedotin ,Regimen ,Treatment Outcome ,030220 oncology & carcinogenesis ,Relapsed refractory ,Lymphoma, Large B-Cell, Diffuse ,Neoplasm Recurrence, Local ,business ,Diffuse large B-cell lymphoma ,030215 immunology - Abstract
The efficacy of polatuzumab vedotin in relapsed/refractory diffuse large B-cell lymphoma outside clinical study are undetermined. This retrospective study examined the efficacy and safety of polatuzumab vedotin administered in real life settings. Forty-seven patients, 31 with
- Published
- 2020
7. Author response for 'Radiotherapy in mantle cell lymphoma: a literature review'
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Nadav Sarid, Sharon Ben Barouch, John Kurvilla, Richard W. Tsang, and Eva Yashphe
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Radiation therapy ,business.industry ,medicine.medical_treatment ,medicine ,Cancer research ,Mantle cell lymphoma ,business ,medicine.disease - Published
- 2019
8. Hodgkin lymphoma of the gastrointestinal tract in patients with inflammatory bowel disease: Portrait of a rare clinical entity
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Aaron Polliack, Yair Herishanu, Catherine Tang, Merav Barzilai, Ron Ram, Nadav Sarid, Chava Perry, and Irit Avivi
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Adult ,Male ,Epstein-Barr Virus Infections ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Disease ,Inflammatory bowel disease ,Gastroenterology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Aged ,Gastrointestinal Neoplasms ,Gastrointestinal tract ,Chemotherapy ,business.industry ,Histology ,Immunosuppression ,Hematology ,Middle Aged ,Inflammatory Bowel Diseases ,medicine.disease ,Hodgkin Disease ,Ulcerative colitis ,Lymphoma ,Oncology ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,business - Abstract
Patients with inflammatory bowel disease (IBD) on immunosuppression are at risk of developing lymphoma, particularly primary gastrointestinal (GI) tract non-Hodgkin lymphoma. Primary GI Hodgkin lymphoma (HL) in this setting, however, is rare and poorly defined. Here we review the available literature and also report a patient with Crohn's disease (CD) who developed GI HL. Our search yielded 12 single case studies and 7 case series involving 22 patients published between 1978-2016. Twenty-one (91%) patients had CD, and 2 had ulcerative colitis. The median age at lymphoma diagnosis was 39 years, and 18 (78%) patients were males. HL was diagnosed at a median of 8 years after IBD detection and 2 years after commencing immunosuppression. HL had a predilection (80%) to involve the inflamed GI site and the histological subtype was mixed cellularity in 65% of cases. In-situ hybridization for Epstein-Barr virus (EBV)-encoded RNA was positive in all documented cases. HL was diagnosed in stages I, II, IV in 35%, 20% and 45% of the patients, respectively. Notably, 66% of patients with advanced disease had liver involvement. Immunosuppression was stopped in most (69%) patients at HL diagnosis. Treatment used was either chemotherapy only, surgery followed by chemotherapy, or surgery alone in 50%, 33% and 16% of cases, respectively. Four patients had an IBD flare during HL remission. Patients with IBD who develop GI HL have distinct characteristics; male sex, predominance of CD, preference to develop in inflamed sites, mixed cellularity histology, EBV positivity, and a unique spread to the liver pattern.
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- 2018
9. The risk of bleeding in patients receiving ibrutinib combined with novel direct oral anticoagulants
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Michal Ariela Raz, Sharon Ben Baruch, Irit Avivi, Jon E. Arnason, Chava Perry, Lev Shvidel, Nadav Sarid, Varon Dvid, Yair Herishanu, Osnat Bairey, Ilya Kirgner, and Ariel Aviv
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Oncology ,Male ,medicine.medical_specialty ,Immunology ,Hemorrhage ,Biochemistry ,Dabigatran ,chemistry.chemical_compound ,Piperidines ,Internal medicine ,Medicine ,Humans ,In patient ,Aged ,Aged, 80 and over ,Rivaroxaban ,business.industry ,Incidence (epidemiology) ,Adenine ,Warfarin ,Anticoagulants ,Atrial fibrillation ,Retrospective cohort study ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Pyrimidines ,chemistry ,Ibrutinib ,Pyrazoles ,Apixaban ,Female ,business ,medicine.drug - Abstract
Introduction: Ibrutinib, an irreversible inhibitor of Bruton's tyrosine kinase, is an established therapeutic agent in a variety of B-cell lymphoproliferative disorders. Ibrutinib induces platelet dysfunction and concurrent treatment with ibrutinib and warfarin was shown to significantly increase the risk of bleeding. The current study was designed to investigate the safety of direct oral anticoagulants (DOACs) in patients receiving ibrutinib, considering their expanding employment together with the lack of data regarding their safety in patients receiving ibrutinib. Methods: We conducted a retrospective cohort study to evaluate risks of major bleeding in patients with B-cell lymphoproliferative disorders (CLL, MCL, DLBCL, MZL or WM) that were treated with ibrutinib and DOACs but without concurrent antiplatelet therapy, between January 2010 and October 2018 in 5 participating centers. Patient medical charts were reviewed for demographic parameters, comorbidities, ibrutinib dosage, DOACs dosage (including the adjustment for renal function), blood count and chemistry tests, bleeding site and grade. Results: The study included 30 patients, median age at starting concurrent administration of ibrutinib and DOACs was 71.58 years (range 50.9-88.2). Most patients were treated for CLL (n=18, 60%) and MCL (n=8, 26%). The most common daily doses of ibrutinib were 420 mg and 560 mg in 63.3% and 30% of patients respectively. None of the patients received an additional antiplatelet agent. Twenty-three patients were treated with apixaban (76.7%), 4 with rivaroxaban (13.3%) and 3 (10%) with dabigatran. The main indications for DOACs were atrial fibrillation and VTE (venous thromboembolism). The median follow-up after initiation of the ibrutinib-DOAC combination was 13.4 months (range 1.8-47.9 months). Bleeding was reported in 22 patients (73.3%), mostly mucocutaneous (n=12, 40%) and gastrointestinal tract (n=7, 23.3%), followed by CNS bleeding (n=4, 13.3%). Mucocutaneous bleedings were all grade 1-2 and gastrointestinal tract and CNS bleeding events were grade 1-4. Major bleeding events, defined as grade 3 or 4, occurred in 5 patients (16.6%) and did not result in death of any of the patients. The median time for bleeding following ibrutinib-DOAC initiation was 5.6 months. Over a follow-up period of 21 months of combined treatment, the incidence of bleeding events (of all grades) increased to 75% (Figure 1). Incidence of bleeding events (including all grades) was quite similar between all DOAC subtypes (73.9% with apixaban, 75% with rivaroxaban and 66.7% with dabigatran). No statistically significant predictors for increased risk of bleeding in patients receiving ibrutinib combined with DOACs were detected. Ibrutinib was stopped in 8 patients (26.7%) due to grade 1 to 4 bleeding events and was re-initiated in 6 patients, resulting in recurrent grade 3 and 4 bleeding events in 2 patients. Conclusions: Concurrent administration of DOACs and ibrutinib appears to be feasible. However, risk of bleeding is not neglectable, and treatment resumption in patients that experienced a significant bleeding event should be considered with caution. Disclosures Arnason: Celgene/Juno: Consultancy; Regeneron Pharmaceuticals, Inc.: Consultancy. Herishanu:Roche: Honoraria; AbbVie: Honoraria; Janssen: Honoraria.
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- 2019
10. CT findings are highly predictive for perforation in patients with diffuse large B-cell lymphoma involving the intestines
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Nadav Sarid, Yair Herishanu, Irit Avivi, Achiude Bendet, Sharon Z. Adam, Adi Sherban, and Chava Perry
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Male ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Pathology ,Perforation (oil well) ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,medicine ,Humans ,In patient ,Ct findings ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,Lymphoma ,Intestines ,030104 developmental biology ,Increased risk ,Oncology ,Intestinal Perforation ,030220 oncology & carcinogenesis ,Female ,Lymphoma, Large B-Cell, Diffuse ,Radiology ,medicine.symptom ,Tomography, X-Ray Computed ,Complication ,business ,Diffuse large B-cell lymphoma - Abstract
Patients with diffuse large B-cell lymphoma (DLBCL) presenting with intestinal involvement are prone to develop perforation. Identification of those who are at high risk for this complication would enable a rational-based decision regarding preemptive surgery. Although computed tomography (CT) is widely used at diagnosis, data regarding its ability to predict intestinal perforation are scanty. We performed a retrospective single-center study, including all consecutive DLBCL patients presented with intestinal involvement, assessing predictors for perforation with an emphasis on CT-related parameters. Forty-nine patients were included, 43 (88%) underwent CT scan at diagnosis. Ten patients (20%) developed intestinal perforation. A univariate regression analysis found increased risk among patients with a concentric, transmural lesion, and a longer involved intestinal segment. In conclusion, CT scan results can define patients with DLBCL and intestinal involvement who are at risk for perforation, suggesting that a preemptive surgical resection should be considered in these cases.
- Published
- 2017
11. Anti-CD20-Mediated B Cell Depletion Is Associated with Reduced Osteoclastogenic Signals and Bone Mass Preservation: Clinical Observation in Patients with Follicular Lymphoma Supplemented By Animal Studies in a Murine Model
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Moshe Mittelman, Ofer Sadovnic, Nadav Sarid, Anton Gorodov, Howard S. Oster, Yankel Gabet, Zamzam Awida, Drorit Neumann, Nathalie Ben-Califa, Chava Perry, Maria Ibrahim, Tamar Liron, Albert Kolomansky, Irit Kay, and Sahar Hiram-Bab
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Oncology ,medicine.medical_specialty ,Bone preservation ,Bone density ,business.industry ,Immunology ,Follicular lymphoma ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Bone resorption ,Bone remodeling ,Immunophenotyping ,medicine.anatomical_structure ,Internal medicine ,medicine ,Rituximab ,Bone marrow ,business ,medicine.drug - Abstract
Background and aims: Immunotherapy with anti-CD20-specific antibodies (e.g. rituximab), has become the standard of care for B cell lymphoproliferative disorders and many autoimmune diseases. Despite previously demonstrated role for B cells in bone metabolism, the effect of anti-CD20-mediated B cell depletion on bone mass in human patients has not been thoroughly studied. For example, in rheumatological patients the effect of rituximab on bone mass yielded conflicting results, while in lymphoma patients it has not yet been described. Here, we describe the effect of treatment with anti-CD20-specific antibodies on bone mass in a cohort of patients with follicular lymphoma and propose a plausible mechanism using murine model. Methods: To assess the effect of rituximab on bone mass in lymphoma patients, we retrospectively studied the bone mass in patients with follicular lymphoma (FL) during the maintenance phase of chemoimunotherapy, i.e. when rituximab is administered as monotherapy. FL patients on no maintenance (historical controls) or patients with marginal zone lymphoma were include as a control group. Cross-sectional X-ray imaging (CT/PET-CT), performed at the completion of the induction phase and 6-12 months thereafter, were used to serially assess bone density. Wild-type female C57BL/6J mice and mouse anti-mouse CD20 antibody (Genentech) were used for the animal experimental system. Murine bone structure was assessed by the microCT method. Immunophenotyping of the bone marrow (BM), spleen and peripheral blood cells was performed. ELISA and "real-time" quantitative PCR were used to measure the levels of key mediators of bone remodeling, e.g. RANKL, OPG and TNFα. Standard osteoclastogenic assay was used to assesses the osteoclastogenic potential of BM cells. Results: Rituximab treatment prevented the decline in bone mass observed in patients who did not receive active maintenance therapy, both in the lumbar spine (-2.6% vs -8%) and femoral head (-0.5% vs -5.1%) (n=12 patients in each group, p Conclusions: While many lymphoma patients may suffer from bone loss due to advanced age and glucocorticoid administration, our data suggest additional favorable effect of anti-CD20 treatment in bone preservation. Importantly, our murine studies indicate that B cell depletion has a direct effect on bone remodeling, primarily by reducing the osteoclastogenic signals, thus potentially diminishing bone resorption. This novel unrecognized effect should be taken into consideration when maintenance treatment is considered. MM and DN contributed equally to this work. Figure Disclosures No relevant conflicts of interest to declare.
- Published
- 2020
12. Reduced-dose ICE chemotherapy ± rituximab is a safe and effective salvage therapy for fit elderly patients with diffuse large B-cell lymphoma
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Lili Gibstein, Nadav Sarid, Irit Avivi, Erel Joffe, Aaron Polliack, Yair Herishanu, and Chava Perry
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Male ,Cancer Research ,medicine.medical_specialty ,Salvage therapy ,Comorbidity ,Kaplan-Meier Estimate ,Transplantation, Autologous ,Gastroenterology ,Carboplatin ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Autologous transplantation ,Ifosfamide ,Progression-free survival ,Etoposide ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,Salvage Therapy ,business.industry ,Age Factors ,Hematology ,medicine.disease ,Combined Modality Therapy ,Surgery ,Regimen ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Female ,Rituximab ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,Stem Cell Transplantation ,030215 immunology ,medicine.drug - Abstract
The risk of developing non-Hodgkin lymphoma increases with age, yet elderly patients are under-represented in clinical trials. Here, we evaluate a combination regimen including ifosfamide, carboplatin and etoposide with or without rituximab (ICE ± R) in 32 fit elderly patients (median age 75.6 years) with relapsed or refractory diffuse large B-cell lymphoma. ICE ± R was generally administered in reduced doses and was well tolerated. The overall response rate (ORR) was 53.1% with a complete response (CR) rate of 40.6%. The median progression free survival (PFS) and overall survival (OS) were 3.9 and 17.0 months, respectively. Patients who responded to ICE ± R achieved median PFS of 47.2 months and OS of 78.9 months. Patients ineligible for autologous transplantation who responded to ICE ± R were treated with additional cycles, and achieved a median PFS of 18.9 months and OS of 21.7 months. Previous response to first-line therapy was the strongest predictor of response, PFS and OS to second-line treatment.
- Published
- 2015
13. Outcome of Relapsed DLBCL Patients, Treated with Polatuzumab-BR or Polatuzumab-R: Real Life Data
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Shimrit Ringelstein Harlev, Najib Dally, Chava Perry, Vladimir Vainstein, Neta Goldschmidt, Orit Sofer, Nadav Sarid, Noam Benyamini, Ron Ram, Uri Abadi, Elena Ribakovsky, Merav Leiba, Yair Herishanu, Odit Gutwein, Anatoly Nemets, Irit Avivi, Abraham Avigdor, Yafit Segman, and Kalman Filanovsky
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Bendamustine ,Oncology ,Univariate analysis ,medicine.medical_specialty ,Palliative care ,business.industry ,Immunology ,Follicular lymphoma ,Cell Biology ,Hematology ,Neutropenia ,medicine.disease ,Biochemistry ,Internal medicine ,medicine ,Rituximab ,business ,Diffuse large B-cell lymphoma ,Febrile neutropenia ,medicine.drug - Abstract
Introduction The therapeutic options for diffuse large cell B cell lymphoma (DLBCL) patients (pts) that fail to respond/relapse after≥2 treatment regimens are limited. The SCHOLAR-1 study reported an overall response/ complete remission (ORR/CR) rates of 26%/ 7% with a median overall survival (OS) of 6.3 months in chemorefractory and early relapsing DLBCL pts. Polatuzumab vedotin (Pola) is a conjugated antibody that delivers the microtubule inhibitor MMAE to CD79b-expressing cells. Polatuzumab administered in combination with Bendamustine-Rituximab (P-BR) has been recently approved by the FDA for pts with relapsed/refractory (R/R) DLBCL that failed to respond≥2 prior therapies. The current study investigated the tolerability and efficacy of Pola mainly with BR, in DLBCL pts, treated through a compassionate program after failing ≥2 prior regimens. Methods Data of all pts with consecutive R/R DLBCL, treated with Pola-BR or Pola-R (2-8 cycles) in 11 Israeli centers between 6/2018 and -5/2019 were analyzed. Inclusion criteria for this study were: R/R DLBCL (denovo and transformed follicular lymphoma [t-FL]), age ≥ 18 years, ≥ 2 prior treatments. We evaluated pt characteristics, treatment details and toxicities, overall response and CR rates, progression free survival (PFS) and OS. Cox regression model was used to define factors affecting outcomes. Results 34 patients- (denovo DLBCL, n=24 and t-FL, n=10 ⌈50% -non CGB and 50% - GCB type⌉) were included. Median age at Pola administration was 65.5 (range 60-72) years. Stage ≥3 disease was recorded in 88% and IPI ≥3 in 73.5%. Median prior lines was 3 (range 3-5); including anthracyclines and rituximab in 100% and cisplatin-based regimens in 91%. 32% relapsed after ASCT and 9% after CART infusion. 53% had primary refractory disease, 29% had refractory relapse and 18% had prior sensitive relapse. 22 pts received Pola-B, mostly with Rituximab (n=19), and 12 received Pola-R. In 5 pts, Pola-based regimen was used as a bridge for Allo SCT (all responded CR, n=4 and PR, n=1) and in 6 as a bridge to CARTs (all responded CR n=1, PR n=2, SD n=3). Median number of Pola B cycles was 3 (3-5) and median Pola-R cycles was 4 (3-6). Median B dose per cycle was 90 mg/m2 (45-90). GCSF was used in 47%. Early treatment discontinuation due to progressive disease (PD) occurred in 8 (23%) of the entire cohort: 23% of Pola-B pts and 25% of Pola-R pts. Safety: Hematological AEs grade 3-4, reported with Pola- B vs Pola-R were: neutropenia (45.5.% vs 33%), thrombocytopenia (25% vs 8%) and anemia (23% vs 17%). Infections were recorded in 41% and 36% of Pola-B pts and Pola-R respectively. Neutropenic fever was reported in 36% in Pola-B pts and none in Pola-R. Pulmonary infections were recorded in 33.3% and 27.3% of Pola-B and Pola-R pts respectively, resulting in death in one pt. Peripheral neuropathy occurred in 18% of Pola- B pts (grade ≤2) vs 8% with Pola -R. Hospitalization due to AEs was recorded in 41% of Pola-B vs 25% of Pola-R. Pola dose reduction due to AE was reported in 1 pt (8%) in the Pola-R. Efficacy: ORR for the entire cohort was 65%, including 38% CRs and 27% PRs. 12% pts attained SD and 23% experienced PD. ORR was higher in non-GCB than in GCB pts 80% vs 43% (p=0.036). Median follow up of the entire cohort from Pola administration was 4.4 months (range 0.6-11.4). 6 months projected OS and PFS were 83% and 63%, respectively. Post Pola treatment in pts that failed to respond/Relapsed post pola: 8 patients had PD; 3 died from progression, 1-CART, 1-Allo SCT, 2-paliative care and 1-unknown. Additional 5 pts progressed during follow up; 4-CART and 1-palliative care. 1 patient continues Pola treatment after achieving SD. Univariate analysis for factors predicting PFS and OS GCB type (HR-1.816, P=0.055), Primary refractory vs relapsed disease (HR-1.507, p=0.049) and a higher number of prior lines since diagnosis (HR-1.35, p=0.079) tended to be associated with shorter time to progression. T-FL vs denovo DLBCL was associated with decreased OS (p=0.008). Data of 60 patients, including pts treated recently, therefore, not evaluable at the time of abstract submission, would be presented at ASH. Conclusions The toxicity of Pola-based regimen was relatively low. Pola based treatment provided an encouraging PFS and OS in pts with R/R DLBCL that failed to respond ≥2 prior therapies, treated in a real-life setting. Primary refractory disease, higher number prior lines and t-FL vs denovo DLBCL were associated with inferior outcome. Figure Disclosures Herishanu: Roche: Honoraria; AbbVie: Honoraria; Janssen: Honoraria.
- Published
- 2019
14. Retrospective analysis of efficacy and safety of third-line chemotherapy for metastatic colorectal cancer among elderly patients receiving targeted therapy in early lines
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Einat Shacham-Shmueli, Nadav Sarid, and Ravit Geva
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Oncology ,third-line chemotherapy ,Chemotherapy ,medicine.medical_specialty ,business.industry ,Colorectal cancer ,medicine.medical_treatment ,metastatic colorectal cancer ,Disease ,Neutropenia ,medicine.disease ,elderly patients ,Symptomatic relief ,Targeted therapy ,Internal medicine ,Medicine ,Stage (cooking) ,Geriatrics and Gerontology ,business ,Survival rate - Abstract
Background/PurposeAbout one-half of metastatic colorectal cancer (MCRC) patients are ≥70 years of age. There is uncertainty regarding the benefit patients derive from advanced chemotherapy lines. In this study, we aim to evaluate the efficacy and safety of third-line chemotherapy treatments among MCRC patients.MethodsConsecutive patients 70 years or older at the time of diagnosis of metastatic disease who received third-line chemotherapy at the Tel-Aviv Sourasky Medical Center between the years 2000–2009 were collected. Data on demographics, stage of disease, treatment lines and oncological outcomes were extracted from their medical files.ResultsOnly 34 out of 63 patients (54%) available patients received third-line treatments. The (median) age of all patients, third-line patients and the remaining patients, were similar (74.5, 74 and 75.3 years, respectively, P = NS). Following third-line treatments, only 9% had a partial response, and the disease was stable in 29% of patients seen. Thirteen weeks is the median duration of third-line treatments. Only three patients had symptomatic relief. Importantly, 15 patients (44%) required dose reduction or treatment delay due to toxicity (neutropenia or thrombocytopenia). The median survival (mOS) is 9 months for patients with first-line treatment, 19 months for second-line treatment and 37 months for third-line treatment (Log Rank
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- 2015
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15. Treatment and prognosis of stage I follicular lymphoma in the modern era - does PET matter?
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Lev Shvidel, Anat Gafter-Gvili, Nadav Sarid, Irit Avivi, Najib Dally, Natalia Kreiniz, Ora Paltiel, Netanel A. Horowitz, Odit Gutwein, Chezi Ganzel, Chava Perry, Ronit Gurion, Ron Ram, Ohad S. Bentur, Moshe E. Gatt, Yair Herishanu, and Pia Raanani
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0301 basic medicine ,Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Follicular lymphoma ,03 medical and health sciences ,0302 clinical medicine ,Fluorodeoxyglucose F18 ,Internal medicine ,Positron Emission Tomography Computed Tomography ,medicine ,Humans ,Survival rate ,Lymphoma, Follicular ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,Stage I Follicular Lymphoma ,medicine.diagnostic_test ,Radiotherapy ,business.industry ,Retrospective cohort study ,Hematology ,Middle Aged ,medicine.disease ,Lymphoma ,Radiation therapy ,Survival Rate ,030104 developmental biology ,Positron emission tomography ,030220 oncology & carcinogenesis ,Rituximab ,Female ,Radiopharmaceuticals ,Nuclear medicine ,business ,medicine.drug ,Follow-Up Studies - Abstract
Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma. Patients with stage I disease are usually treated with radiotherapy (RT). In previous studies, mostly from the pre positron emission tomography-computed tomography (PET-CT) era, the 5 year progression-free survival (PFS) and overall survival (OS) rates of stage I disease were 60-80% and 80-93%, respectively. This study retrospectively evaluated the outcome of stage I FL which was treated with involved field RT in the PET-CT era between 2002 and 2015. Ninety-one patients were enrolled. Five year PFS and OS rates were 73% and 97%, respectively. Relapse occurred in 19 (21%) patients, 74% occurring outside the radiation field. In conclusion, PET-CT staging of clinical stage I FL may contribute to the improved prognosis in patients treated with RT compared to historical cohorts, possibly due to better identification of "genuine" stage I disease.
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- 2017
16. Dividing plasma cells in the cerebrospinal fluid of a patient with refractory multiple myeloma
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Nadav Sarid and Ben-Zion Katz
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Immunoglobulin A ,Male ,Pathology ,medicine.medical_specialty ,Cytodiagnosis ,Immunology ,Plasma Cells ,Mitosis ,Biochemistry ,Cerebrospinal fluid ,medicine ,Humans ,Multiple myeloma ,Lenalidomide ,Aged ,Cerebrospinal Fluid ,biology ,business.industry ,Incidence ,Refractory Multiple Myeloma ,Cell Biology ,Hematology ,medicine.disease ,Thalidomide ,biology.protein ,business ,Multiple Myeloma ,medicine.drug - Abstract
[Figure][1] A 72-year-old man presented in an acutely confused state. He had been diagnosed with immunoglobulin A κ, 17p-deleted multiple myeloma (MM) 3 years prior. He had since received numerous lines of treatment, including several immunomodulatory agents (thalidomide, lenalidomide
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- 2016
17. The Value of PET/CT in Detecting Bone Marrow Involvement in Patients With Follicular Lymphoma
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Nadav Sarid, Erel Joffe, Odelia Amit, Yair Herishanu, Irit Avivi, Chava Perry, Einat Even-Sapir, Hedva Lerman, Mikhail Kesler, and Jonathan Ben-Ezra
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Male ,Biopsy ,Follicular lymphoma ,Standardized uptake value ,Diagnostic Accuracy Study ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Fluorodeoxyglucose F18 ,Predictive Value of Tests ,Medicine ,Humans ,False Positive Reactions ,Lymphoma, Follicular ,Retrospective Studies ,PET-CT ,medicine.diagnostic_test ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Lymphoma ,medicine.anatomical_structure ,ROC Curve ,030220 oncology & carcinogenesis ,Predictive value of tests ,Bone marrow neoplasm ,Positron-Emission Tomography ,Female ,Bone marrow ,business ,Nuclear medicine ,Bone Marrow Neoplasms ,Tomography, X-Ray Computed ,Research Article - Abstract
Follicular lymphoma (FL) is the 2nd most common type of lymphoma diagnosed in the Western World. Bone marrow (BM) involvement is an adverse prognostic factor in FL, routinely assessed by an arbitrary biopsy of the iliac crest. This study was aimed to investigate the role of positron emission tomography/computed tomography (PET/CT) in identifying BM involvement by FL. In this retrospective, single-center study we reviewed the records of consecutive patients with FL at diagnosis or relapse who underwent staging/restaging workup visual assessment of BM uptake was categorized as either normal, diffusely increased, or focally increased. Quantitative BM fluorine-18-fluro-deoxyglucose (FDG) uptake was measured using mean standardized uptake value (BM-SUVmean). The diagnosis of BM involvement was based on either BM histological findings or disappearance of increased uptake at end-treatment PET/CT in patients who responded to treatment. Sixty eight cases with FL were included. Sixteen (23.5%) had BM involvement, 13 (19.1%) had a biopsy proven involvement, and 3 (4.4%) had a negative BM biopsy, but increased medullary uptake that normalized post-treatment. BM FDG uptake in these patients was diffuse in 8 (50%) and focal in 8 (50%). Focal increased uptake was indicative of BM involvement; however, diffuse uptake was associated with 17 false positive cases (32.7%). Overall, visual assessment of BM involvement had a negative predictive value (NPV) of 100% and a positive predictive value (PPV) of 48.5%. On a quantitative assessment, BM-SUVmean was significantly higher in patients with BM involvement (SUVmean of 3.7 [1.7–6] vs 1.4 [0.4–2.65], P 2.7 had a PPV of 100% for BM involvement (sensitivity of 68%), while BM-SUVmean
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- 2016
18. Outcome predictors in elderly Hodgkin's lymphoma patients placeholder
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S. Peled, Chava Perry, David Lavie, Irit Avivi, N. Dally, Nadav Sarid, D. Eldad, E. Paran, Z. Neuman, Odit Gutwein, Yair Herishanu, Boaz Nachmias, and Ohad S. Bentur
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Hematology ,General Medicine ,business ,Hodgkin's lymphoma ,medicine.disease ,Outcome (game theory) - Published
- 2017
19. Predictive value of TP53 fluorescencein situhybridization in cytogenetic subgroups of acute myeloid leukemia
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Ruth Shomrat, Nadav Sarid, Sigal Tavor, Rachel Rothman, Nadia Voskoboinik, Elizabeth Naparstek, Tamar Golan, Avi Orr-Urtreger, and Ben-Zion Katz
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Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Monosomy ,Pathology ,Myeloid ,Antineoplastic Agents ,Biology ,Predictive Value of Tests ,Internal medicine ,Complex Karyotype ,medicine ,Humans ,neoplasms ,In Situ Hybridization, Fluorescence ,Survival analysis ,Aged ,Aged, 80 and over ,medicine.diagnostic_test ,Myeloid leukemia ,Hematology ,Middle Aged ,medicine.disease ,Survival Analysis ,Leukemia, Myeloid, Acute ,Leukemia ,Treatment Outcome ,medicine.anatomical_structure ,Karyotyping ,Predictive value of tests ,Female ,Tumor Suppressor Protein p53 ,Gene Deletion ,Fluorescence in situ hybridization - Abstract
Acute myeloid leukemia (AML) with a complex karyotype (CK) has frequent alterations in TP53 and a very poor prognosis. We examined whether a prompt and simple fluorescence in situ hybridization (FISH) analysis for 17p13 deletion at diagnosis has a predictive value for response to therapy and overall survival in subgroups of AML. In 15 patients with a normal karyotype the TP53 FISH analysis was normal, whereas in 16 patients with CK 75% had only one copy of the TP53 allele. The deletion was also detected in 33% of six patients with monosomy or partial monosomy of chromosome 5, 7, 9, or 12. This loss of TP53 correlated significantly with a poor response to chemotherapy, and the median survival time of these patients was shorter. TP53 FISH analysis carried out at diagnosis has a predictive value with respect to chemotherapy response and can therefore facilitate a rapid decision on treatment strategies.
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- 2011
20. High response rate for treatment with gemtuzumab ozogamicin and cytarabine in elderly patients with acute myeloid leukemia and favorable and intermediate-I cytogenetic risk
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Nadav Sarid, Sigal Tavor, Uri Rozovski, Ilya Kirsner, Lili Gibstein, Freddy Aviv, Elizabeth Naparstek, and Einam Rahamim
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Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Myeloid ,Gemtuzumab ozogamicin ,medicine.medical_treatment ,Antibodies, Monoclonal, Humanized ,Disease-Free Survival ,Cytogenetics ,Risk Factors ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Aged ,Retrospective Studies ,Aged, 80 and over ,Chemotherapy ,Performance status ,business.industry ,Mortality rate ,Remission Induction ,Cytarabine ,Myeloid leukemia ,Hematology ,Middle Aged ,medicine.disease ,Gemtuzumab ,Leukemia ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Aminoglycosides ,Immunology ,Female ,business ,medicine.drug - Abstract
Recent studies have reevaluated whether gemtuzumab ozogamicin (GO) improves the outcome of acute myeloid leukemia (AML) in elderly patients. Over 5 years, we treated 16 elderly patients with AML with GO and cytarabine. A high response rate, prolonged survival, and low toxicity were observed in the favorable and intermediate-I genetic groups of AML. Our study raises the issue about the optimal protocol for these patients. Background: The benefit of gemtuzumab ozogamicin (GO) in combination with chemotherapy as frontline therapy in patients with acute myeloid leukemia (AML) is still debated. Patients and Methods: We evaluated the safety and efficacy of low-dose GO with cytarabine in elderly patients with newly diagnosed AML. Over the past 5 years, we have treated 16 elderly patients with AML (64-82 years) with GO (3 mg/m 2 ) followed by continuous infusion of cytarabine (100 mg/m 2 ) for 7 days. Results: Complete remission (CR) was achieved in 68.8% of patients; however, this was true only in patients in the favorable or intermediate-I cytogenetic risk groups. Of the 12 patients with AML in the favorable and intermediate-I genetic groups, 11 (91.7%) achieved CR. By comparison, of all 4 patients in the intermediate-II or adverse genetic groups, none of the patients achieved CR (P .003). The median disease-free survival and overall survival (OS) was 10.9 and 18.8 months, respectively, for patients who achieved CR. The estimated median survival was 15 months in the favorable and intermediate-I cytogenetic groups and only 4.4 months in the intermediate-II and unfavorable risk groups (P .008). The toxicity profile was also manageable in patients with AML who were mainly older than 70 years with good performance status (PS). The 8-week mortality rate was 6.25%, which is relatively low in this high-risk group of patients. These data are in line with results from 2 randomized trials suggesting that the addition of low-dose GO should be further investigated to reevaluate its role in selected elderly patients with AML and raises the issue of the optimal protocol.
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- 2012
21. Acute myeloid leukemia with 11q23/MLL rearrangement after ‘FCR’ regimen for chronic lymphocytic leukemia
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Meirav Shpringer, Lili Gepstein, Jonathan Canaani, Elizabeth Naparstek, Yair Herishanu, Chava Perry, Rinat Eshel, Nadav Sarid, Rachel Rothman, Nili Dezorella, Irit Solar, and Aaron Polliack
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business.industry ,FCR Regimen ,Chronic lymphocytic leukemia ,Cancer research ,Medicine ,Myeloid leukemia ,Hematology ,General Medicine ,Mll rearrangement ,business ,medicine.disease - Published
- 2012
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